Exploring the Therapeutic Potential of Noncoding RNAs in Alzheimer's Disease.

IF 1 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Protein and Peptide Letters Pub Date : 2024-11-15 DOI:10.2174/0109298665335550241011080252

Siddhant Tripathi, Yashika Sharma, Dileep Kumar

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Abstract

Despite significant research efforts, Alzheimer's disease (AD), the primary cause of dementia in older adults worldwide, remains a neurological challenge for which there are currently no effective therapies. There are substantial financial, medical, and personal costs associated with this condition.Important pathological features of AD include hyperphosphorylated microtubule-associated protein Tau, the formation of amyloid β (Aβ) peptides from amyloid precursor protein (APP), and continuous inflammation that ultimately results in neuronal death. Important histological markers of AD, amyloid plaques, and neurofibrillary tangles are created when Aβ and hyperphosphorylated Tau build-up. Nevertheless, a thorough knowledge of the molecular players in AD pathophysiology is still elusive. Recent studies have shown how noncoding RNAs (ncRNAs), including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), regulate gene expression at the transcriptional and posttranscriptional levels in a variety of diseases, including AD. There is increasing evidence to support the involvement of these ncRNAs in the genesis and progression of AD, making them promising as biomarkers and therapeutic targets. As a result, therapeutic approaches that target regulatory ncRNAs are becoming more popular as potential means of preventing the progression of AD. This review explores the posttranscriptional relationships between ncRNAs and the main AD pathways, highlighting the potential of ncRNAs to advance AD treatment. In AD, ncRNAs, especially miRNAs, change expression and present potential targets for therapy. MiR-346 raises Aβ through APP messenger Ribonucleic Acid (mRNA), whereas miR-107 may decrease Aβ by targeting beta-site amyloid precursor protein cleaving enzyme 1 (BACE1). They are promising early AD biomarkers due to their stability in cerebrospinal fluid (CSF) and blood. Furthermore, additional research is necessary to determine the role that RNA fragments present in AD-related protein deposits play in AD pathogenesis.

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探索非编码 RNA 在阿尔茨海默病中的治疗潜力。

阿尔茨海默病（AD）是全球老年人痴呆症的主要病因，尽管研究人员付出了巨大努力，但它仍然是神经系统的一大难题，目前尚无有效的治疗方法。阿尔茨海默病的重要病理特征包括微管相关蛋白 Tau 的高磷酸化、由淀粉样前体蛋白（APP）形成的淀粉样 β（Aβ）肽以及最终导致神经元死亡的持续炎症。淀粉样蛋白前体蛋白（APP）中的淀粉样β（Aβ）肽会形成淀粉样斑块和神经纤维缠结，而高磷酸化Tau则会形成AD的重要组织学标志物--淀粉样斑块和神经纤维缠结。尽管如此，人们仍然无法彻底了解 AD 病理生理学中的分子角色。最近的研究表明，非编码 RNA（ncRNA），包括微 RNA（miRNA）、长非编码 RNA（lncRNA）和环状 RNA（circRNA），是如何在转录和转录后水平上调控包括 AD 在内的多种疾病的基因表达的。越来越多的证据表明，这些 ncRNAs 参与了注意力缺失症的发生和发展，因此很有希望成为生物标志物和治疗靶点。因此，针对调控ncRNA的治疗方法正变得越来越流行，成为预防AD进展的潜在手段。本综述探讨了 ncRNA 与主要 AD 通路之间的转录后关系，强调了 ncRNA 在促进 AD 治疗方面的潜力。在AD中，ncRNA，尤其是miRNA，会改变表达，成为潜在的治疗靶点。miR-346通过APP信使核糖核酸（mRNA）提高Aβ，而miR-107可能通过靶向β位点淀粉样前体蛋白裂解酶1（BACE1）降低Aβ。由于它们在脑脊液（CSF）和血液中的稳定性，它们是很有希望的早期注意力缺失症生物标志物。此外，有必要开展更多研究，以确定存在于阿德相关蛋白沉积物中的RNA片段在阿德发病机制中的作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Protein and Peptide Letters 生物-生化与分子生物学

CiteScore

2.90

自引率

0.00%

发文量

审稿时长

2 months

期刊介绍： Protein & Peptide Letters publishes letters, original research papers, mini-reviews and guest edited issues in all important aspects of protein and peptide research, including structural studies, advances in recombinant expression, function, synthesis, enzymology, immunology, molecular modeling, and drug design. Manuscripts must have a significant element of novelty, timeliness and urgency that merit rapid publication. Reports of crystallization and preliminary structure determination of biologically important proteins are considered only if they include significant new approaches or deal with proteins of immediate importance, and preliminary structure determinations of biologically important proteins. Purely theoretical/review papers should provide new insight into the principles of protein/peptide structure and function. Manuscripts describing computational work should include some experimental data to provide confirmation of the results of calculations. Protein & Peptide Letters focuses on: Structure Studies Advances in Recombinant Expression Drug Design Chemical Synthesis Function Pharmacology Enzymology Conformational Analysis Immunology Biotechnology Protein Engineering Protein Folding Sequencing Molecular Recognition Purification and Analysis